Controlled release of paclitaxel from a self-assembling peptide hydrogel formed in situ and antitumor study in vitro

Abstract

Jingping Liu1,2, Lanlan Zhang1, Zehong Yang1, Xiaojun Zhao1,31West China Hospital Laboratory of Nanomedicine and Institute for Nanobiomedical Technology and Membrane Biology; 2Key Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, China; 3Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USABackground: A nanoscale injectable in situ-forming hydrogel drug delivery system was developed in this study. The system was based on a self-assembling peptide RADA16 solution, which can spontaneously form a hydrogel rapidly under physiological conditions. We used the RADA16 hydrogel for the controlled release of paclitaxel (PTX), a hydrophobic antitumor drug.Methods: The RADA16-PTX suspension was prepared simply by magnetic stirring, followed by atomic force microscopy, circular dichroism analysis, dynamic light scattering, rheological analysis, an in vitro release assay, and a cell viability test.Results: The results indicated that RADA16 and PTX can interact with each other and that the amphiphilic peptide was able to stabilize hydrophobic drugs in aqueous solution. The particle size of PTX was markedly decreased in the RADA16 solution compared with its size in water. The RADA16-PTX suspension could form a hydrogel in culture medium, and the elasticity of the hydrogel showed a positive correlation with peptide concentration. In vitro release measurements indicated that hydrogels with a higher peptide concentration had a longer half-release time. The RADA16-PTX hydrogel could effectively inhibit the growth of the breast cancer cell line, MDA-MB-435S, in vitro, and hydrogels with higher peptide concentrations were more effective at inhibiting tumor cell proliferation. The RADA16-PTX hydrogel was effective at controlling the release of PTX and inhibiting tumor cell growth in vitro.Conclusion: Self-assembling peptide hydrogels may work well as a system for drug delivery.Keywords: self-assembling peptide, hydrogel, paclitaxel, drug delivery, antitumor